A growing number of children, adolescents, and young adults (CAYA) are suffering from cancer and are surviving after treatment. However, the incidence and long-term overall survival patterns for CAYA cancer survivors over the past 20 years have been underreported. Data from 17 Surveillance, Epidemiology, and End Results (SEER) registries in the United States were analyzed to identify cancer cases in individuals under the age of 25 from 2000 to 2020. A joinpoint regression model was used to analyze the trend of cancer incidence and 5-year survival rate in CAYA. Additionally, we examined the temporal trends of age-standardized cancer incidence and 5-year survival rate from 2000 to 2020. Between 2000 and 2020, there were 129,384 CAYA patients under the age of 25 with cancer (67,873 males and 61,511 females) in the USA. The overall age-standardized incidence rate (ASIR) of CAYA cancer was 19.26 per 100,000 in 2000 and 21.47 per 100,000 in 2020. The incidence rate of CAYA cancer increased over time, with males having a higher incidence rate than females. The most common cancer types were leukemia, lymphoma, brain and other nervous system cancer, endocrine system cancer, and male genital system cancer, which together accounted for more than 60% of CAYA cancer cases. The overall 5-year relative survival rate of CAYA cancer increased from 80.40% (95% CI, 78.84%-81.87%) in 2000 to 87.80% (95% CI, 86.65%-88.86%) in 2015. The 5-year relative survival rate of females under the age of 25 was higher than that of males (89.86% vs. 85.58%). Due to their long life expectancy, CAYA cancer survivors are at particular risk of long-term sequelae from the cancer itself or the therapy applied, especially late sequelae related to reproduction. These issues remain problematic for cancer survivors after entering adulthood, highlighting the need for more efforts and strategies to be directed towards fertility protection for young cancer survivors.